The compound 17.alpha.-acetoxy-11.beta.-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-di ene-3,20-dione, represented by formula I ##STR3## is a well-known steroid, more specifically a 19-norprogesterone, which possesses antiprogestational and antiglucocorticoidal activity. This compound, and a method for its preparation, are described in U.S. Pat. No. 4,954,490.
The method for the preparation of the 19-norprogesterone compound of formula I set forth in the '490 patent is reproduced in FIG. 1. This method begins by converting 3-methoxyesterone 1 to a tetra-ene 2 via the Wittig reaction using ethyl triphenyl phosphonium iodide. The tetra-ene 2 is then hydroxylated using OsO.sub.4 to provide the compound of formula 3. That compound is then reduced using Li/NH.sub.3 to form compound 4, with the latter being subjected to mild acid hydrolysis to form compound 5. Subsequently, compound 5 is subjected to bromination-dehydrobromination to provide a dienone 6. Swern oxidation is then used to convert the dienone 6 to compound 7, with compound 7 being ketalized to provide a ketal 8. The ketal 8 is then epoxidized using m-chloroperbenzoic acid to provide an epoxide 9. The epoxide then undergoes conjugate ring-opening using a copper (I) catalyzed Grignard reagent generated by the reaction of 4-bromo-N,N dimethylaniline with magnesium in the presence of copper (I) to provide compound 10. A single-step hydrolysis/acetylation/dehydration procedure, using H.sub.3 PO.sub.4 /Ac.sub.2 O/HOAc, is then used to convert compound 2- to the desired 19-norprogesterone of formula I (indicated as compound 11 in FIG. 1).
While the foregoing procedure can be used to provide the 19-norprogesterone of formula I, certain drawbacks are inherent therein. More specifically, the foregoing procedure includes processing steps which are hazardous and/or not readily amenable to the preparation of relatively large quantities of the desired 19-norprogesterone, e.g., the use of highly toxic and expensive OsO.sub.4 to affect hydroxylation, effecting Birch reduction using lithium and ammonia, as well as bromination-dehydrobromination and Swern oxidation procedures. Moreover, many of the steps require chromatographic purification for the isolation of the intermediates. Further, the overall yield provided by this known process is relatively low.
In view of the foregoing, a need exists for a relatively safer and more efficient process for the preparation of the 19-norprogesterone of formula I and intermediates thereof, which process is further able to provide those compounds in relatively high quantities and purity levels, as compared to known methods. These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.